Pretreatment PLR Is Preferable to NLR and LMR as a Predictor in Locally Advanced and Metastatic Bladder Cancer.

Background/Aim: Advanced bladder cancer (BC) is associated with an inflammatory nature and poor prognosis Inflammatory biomarkers are potential predictors in BC. We conducted a study to assess the prognostic value of the pretreatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) in advanced bladder cancer. Patients and Methods: A total of 226-patients with muscle-invasive BC (MIBC) were included. Overall (OS) and progression-free survival were estimated using the Kaplan-Meier method and the log-rank test was used for comparison. Univariate and multivariate Cox proportional hazard models were used to determine NLR, PLR, and LMR association with OS. Results: Our patients' median progression-free survival and OS were 12.18 and 15.54 months, respectively. Receiver operating characteristic analysis revealed cut-off values for our chosen inflammatory markers. The patients with high NLR or PLR had inferior median OS compared to their counterparts with lower ratios for both (NLR: 22.51 vs. 9.84 months, respectively, p≤0.001; PLR: 17.68 vs. 14.08 months, respectively, p=0.08). Meanwhile, patients with low LMR had inferior median OS compared to patients with higher LMR (LMR: 20.14 months vs. 10.55 months, respectively, p<0.001). The multivariate Cox regression analysis identified a high PLR as an independent predictive factor of worse OS (hazard ratio=2.774, 95% confidence interval=1.486-5.178, p=0.001) but not NLR or LMR. Conclusion: PLR, C-reactive protein-to-albumin ratio, and serum LDH levels, but not NLR and LMR, may function as independent predictors in patients with advanced BC prior to systemic treatment.

The Effect of Continuing Chemotherapy after Chemoradiotherapy during the Time to Surgery on Tumor Response and Survival for Local Advanced Rectal Cancer.

Aim: The current standard treatment of locally advanced rectal carcinoma is total mesorectal excision and postoperative adjuvant chemotherapy after neoadjuvant concurrent chemoradiotherapy (NCRT). Many studies have shown that pathological complete response (pCR) is an important prognostic factor for patients receiving NCRT. Many studies have therefore been conducted to increase pCR rates by changing the perioperative treatment strategies. Prolonging the chemotherapy time may be a reasonable way to increase the effectiveness of NCRT, pCR, and survival rates. We investigated whether neoadjuvant consolidation chemotherapy had an effect on tumor response and survival. Methods: The data of 163 patients diagnosed with locally advanced rectal carcinoma were evaluated. The data of 107 patients (Group 1) who were radiologically T3-T4 and/or N+ and received chemotherapy after NCRT until their operations were compared with the data of 56 patients (Group 2) who were operated after NCRT. Results: Group 1 patients had tumor and node downstaging. Their pCR was found significantly higher than in Group 2 (p = 0.005). In Group 1 patients with T3, pCR was significantly higher than for those with T4. The elapsed time between NCRT and surgery was significantly longer in patients with pCR (respectively, p = 0.012 and p = 0.008). Conclusion: Neoadjuvant consolidation chemotherapy after NCRT is a safe approach that can lead to higher pathological complete response rates. The time until surgery with neoadjuvant consolidation chemotherapy may provide the chance to follow the patient without surgery in addition to increasing pCR.

Evaluation of Serum microRNA Let-7c and Let-7d as Predictive Biomarkers for Metastatic Pancreatic Cancer.

BACKGROUND: First-line treatments for metastatic pancreatic cancer are chemotherapy regimens consisting of 5-fluorouracil or gemcitabine; however, there are no biomarkers to help determine which patients might benefit from which treatment regimens. We aimed to show that microRNAs let-7c and 7d can be used as independent predictive biomarkers for metastatic pancreatic cancer. METHODS: A total of 55 patients who had first-line chemotherapy with FOLFIRINOX or gemcitabine+capecitabine were included. Patients were divided into groups based on let-7c and let-7d levels and chemotherapy treatment as let-7c-7d high FOLFIRINOX, let7c-7d high gemcitabine+capecitabine, let-7c-7d low FOLFIRINOX, and let-7c-7d low gemcitabine+capecitabine. Blood samples were taken from patients before chemotherapy for microRNA let-7c and 7d analysis. MicroRNA isolation was performed using a miRNeasy Serum/Plasma Kit and identified using spectrophotometric measurements. After isolation, microRNA was converted to cDNA using a microRNA cDNA Synthesis Kit with poly (A) polymerase tailing. The expression of microRNA was examined using quantitative real-time polymerase chain reaction. RESULTS: The overall survival of patients who received FOLFIRINOX treatment with a high let-7c-7d level was statistically significantly longer than those who received gemcitabine+capecitabine with a high let-7c-7d level. In addition, patients with low let-7c expression receiving FOLFIRINOX progressed significantly 2.104 times earlier than patients with high let-7c expression receiving FOLFIRINOX. CONCLUSION: The serum MicroRNA let-7c level was found to be an independent predictive biomarker in the FOLFIRINOX treatment group.

Human Epidermal Growth Factor Receptor 2-Targeting Approaches for Colorectal Cancer: Clinical Implications of Novel Treatments and Future Therapeutic Avenues.

The treatment paradigm for colorectal cancer (CRC) has changed significantly over the past decade with targeted therapeutics. Human epidermal growth factor receptor 2 (HER2) amplification is seen among 3%-4% of patients with metastatic CRC (mCRC). The biological discovery of HER2 amplification in cancer cells has led to practice-changing drug development for several solid tumors, including breast, gastric, and esophageal cancers. HER2 amplification is now highly actionable in CRC with distinct therapeutic combinations, including the combination of monoclonal antibodies and HER2 receptor-specific tyrosine kinase inhibitors, as well as antibody-drug conjugates, that delivers targeted cytotoxic agents. However, it is essential to define the therapeutic role and sequence of these different combinations, some of which are already part of standard clinical practice. In this review article, we discuss recent clinical studies demonstrating the clinical benefits of each distinct therapeutic approach and their impacts on the current management of HER2-amplified mCRC. We also review ongoing clinical trials targeting the HER2 pathway in mCRC and elaborate on novel therapeutic opportunities in this space that may further define the changing paradigm of HER2-targeted therapy for CRC.